What you carry at this position in your DNA and what research says about it.
Metabolic Health: 10/10 evidence, 156 publications.
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Sample genotype (not yours): T/T
Higher Triglycerides and Gout Risk
Two copies of the T allele lead to elevated triglyceride levels and a higher risk of gout and fatty liver disease. However, this genotype is associated with a lower risk of developing type 2 diabetes.
What this genotype means: Elevated blood triglycerides; Increased risk of gout and kidney stones; Lower risk of type 2 diabetes.
Sample genotype (not yours): C/C
Typical Triglycerides and Lower Gout Risk
Two copies of the C allele are associated with healthy triglyceride levels and a lower risk of gout and fatty liver. However, this genotype carries a slightly higher risk of type 2 diabetes.
What this genotype means: Healthy triglyceride levels; Lower risk of gout and kidney stones; Slightly higher risk of type 2 diabetes.
Sample genotype (not yours): T/C
Slightly Higher Triglycerides and Gout Risk
One copy of the T allele is associated with mild elevations in triglycerides and a slightly increased risk of gout. It offers moderate protection against high blood sugar and type 2 diabetes.
What this genotype means: Slightly elevated triglycerides; Mildly increased risk of gout; Moderate protection against type 2 diabetes.
Gene function and biological role
Gene Function: The GCKR gene encodes the glucokinase regulator protein, which plays a critical role in controlling glucose metabolism in the liver [1]. It acts as a competitive inhibitor of glucokinase, the enzyme responsible for the first step of glucose utilization [1]. By regulating glucokinase activity, GCKR helps balance blood sugar levels and hepatic lipid synthesis [2]. Variations in this gene can disrupt this delicate balance, leading to altered blood lipid profiles and metabolic shifts [2].
Variant Impact: The rs1260326 variant is a missense mutation in the GCKR gene that changes the amino acid proline to leucine at position 446 [1]. This structural alteration weakens the regulatory protein's ability to inhibit glucokinase in the liver [3]. As a result, glucokinase remains highly active, accelerating glucose uptake and de novo lipogenesis [3]. This shift drives increased production of triglycerides and fatty acids, contributing to elevated blood lipids and liver fat accumulation [3].
Key Insight: This variant acts as a metabolic double-edged sword, protecting against diabetes while raising triglycerides and gout risk.
Location: GCKR. Chromosome 2 · 2p23.3 · 27.5 Mb
Estimated prevalence by population
Global 12.4%; European 16.8%; African 2.0%; East Asian 24.9%; South Asian 5.9%; Americas 14.0%; Ashkenazi 29.3%; Finnish 13.1%; Middle Eastern 25.7%; Amish 8.5%.
Estimated TT genotype frequency.
Global 41.1%; European 48.4%; African 24.3%; East Asian 50.0%; South Asian 36.7%; Americas 46.8%; Ashkenazi 49.7%; Finnish 46.2%; Middle Eastern 50.0%; Amish 41.3%.
Estimated TC genotype frequency.
Global 46.5%; European 34.8%; African 73.7%; East Asian 25.1%; South Asian 57.4%; Americas 39.2%; Ashkenazi 21.0%; Finnish 40.7%; Middle Eastern 24.3%; Amish 50.2%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
Triglycerides. Evidence: 10/10. Source: PMID 18454146. Increased Levels.
Gout & Uric Acid
Gout. Evidence: 10/10. Source: PMID 25646370. 1.27x Higher Risk.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. Lower Risk.
Organ Systems
Liver Function & Disease
Fatty Liver Disease. Evidence: 10/10. Source: PMID 29385134. Increased Risk.
Kidney Function & Disease
Kidney Stones. Evidence: 10/10. Source: PMID 30975718. 1.08x Higher Risk.
Showing effects for C/C genotype
Triglycerides. Evidence: 10/10. Source: PMID 18454146. Typical Levels.
Gout. Evidence: 10/10. Source: PMID 25646370. Typical Risk.
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. 1.07x Higher Risk.
Fatty Liver Disease. Evidence: 10/10. Source: PMID 29385134. Typical Risk.
Kidney Stones. Evidence: 10/10. Source: PMID 30975718. Typical Risk.
Showing effects for T/C genotype
Triglycerides. Evidence: 10/10. Source: PMID 18454146. Slightly Increased.
Gout. Evidence: 10/10. Source: PMID 25646370. Slightly Increased.
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. Typical Risk.
Fatty Liver Disease. Evidence: 10/10. Source: PMID 29385134. Slightly Increased.
Kidney Stones. Evidence: 10/10. Source: PMID 30975718. Slightly Increased.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
A proline-to-leucine substitution at position 446 in the glucokinase regulator protein impairs its inhibitory function [1]. This impairment keeps liver glucokinase highly active, promoting the conversion of glucose into fatty acids [1]. Consequently, blood triglyceride levels are significantly elevated [2]. The increased metabolic activity also raises serum urate levels, leading to a higher risk of gout and kidney stones [3]. Interestingly, the rapid clearance of glucose into the liver provides robust protection against high blood sugar and type 2 diabetes [4]. Managing dietary fat and fructose intake can help mitigate the elevated lipid and gout risks associated with this genotype.
Elevated blood triglycerides; Increased risk of gout and kidney stones; Lower risk of type 2 diabetes.
Sample genotype: CC (Homozygous)
Maintaining the typical proline residue at position 446 ensures normal regulation of liver glucokinase [1]. This normal regulation prevents excessive conversion of glucose into fatty acids, keeping blood triglycerides in a healthy range [2]. It also keeps serum urate levels lower, significantly reducing the risk of gout and kidney stones [3]. However, because the liver clears glucose less aggressively, fasting blood sugar and insulin levels tend to be slightly higher [4]. This shift results in a modest increase in the risk of developing type 2 diabetes [4]. Regular physical activity and a diet rich in whole grains can help manage blood sugar levels effectively.
Healthy triglyceride levels; Lower risk of gout and kidney stones; Slightly higher risk of type 2 diabetes.
Sample genotype: TC (Heterozygous)
Carrying a single T allele results in a moderate reduction in the glucokinase regulator's ability to control liver glucose uptake [1]. This partial loss of regulation leads to a mild increase in hepatic fat synthesis and circulating triglycerides [2]. Urate levels are also slightly elevated, which can marginally increase the risk of gout over time [3]. On the positive side, the increased liver glucose clearance helps maintain lower fasting blood sugar levels, offering some protection against type 2 diabetes [4]. A balanced diet low in refined carbohydrates can help optimize lipid levels and minimize metabolic risks.
Slightly elevated triglycerides; Mildly increased risk of gout; Moderate protection against type 2 diabetes.
Variants with shared genetic architecture
rs780093 · GCKR Gene · Chr 2 · Triglyceride Levels
rs780094 · GCKR Gene · Chr 2 · Metabolic Health
rs1260333 · GCKR Gene · Chr 2 · Triglyceride Levels
Common genetic variation near MC4R is associated with waist circumference and insulin resistance.
Common variants at 30 loci contribute to polygenic dyslipidemia.
Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.
Content updated August 2026.
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